The viruses that made us

Viruses make their living by breaking into cells and using the machinery and energy in the cell to reproduce. Once inside, some viruses immediately hijack the cell and make copies of themselves which burst out into the world to infect new cells. Other viruses take a staid approach, though. Instead of taking over the cell, they quietly slip a copy of their genes into its DNA. When the cell divides, it copies the newly acquired viral genes along with the rest of its genome. It’s a better deal for the virus, since all of the cell’s descendants will be carrying viral genes which can eventually come out of hiding to commandeer the cell and replicate. A really lucky virus is one that finds itself inside an egg cell. Getting into the DNA of a single cell means getting copied into all of its daughter cells, but getting into the DNA of an egg cell means getting copied into every cell in the organism that grows from the egg…and from there into all of the organism’s offspring. Lucky viruses that succeed in pulling off that trick can still break out and cause trouble, but they can also become integrated into their host’s genome; instead of struggling to reproduce, they can then just kick back and enjoy the ride while we lumber along, making copies of them whenever we make new cells or have children.

It turns out that these viral stowaways aren’t just surprisingly common; they’re also strikingly important. Once incorporated into the host’s genome, the viral genes can become tamed over time, eventually acquiring new functions. Last year, Carl Zimmer wrote about viral genes that have played a critical role in the evolution of mammals. Syncytin is a gene that’s essential for the placenta to properly connect with the uterus. Synctin turned out to be a viral gene that infected our ancestors, but the story doesn’t end there. Mice also have synctin genes which came from viruses, but they’re different from ours; the same is true of rabbits and of carnivorans. In other words, on at least six different occasions ancestral mammals were infected by a virus that got incorporated into their genome and helped them make a placenta.

More recently, Carl has also written about the amazing discovery that viral genes are also important in deciding whether or not cells are totipotent — that is whether they’re able to produce any other kind of cell or only cells like them. Genes are switched on and off by promoters, and researchers had discovered that the promoters of a whole suite of genes that are active specifically in totipotent cells were originally from viruses.

Now, a team of scientists have found that the same is true of primates in general. DNA is packed quite tightly to fit into cells, so it has to be partially unfolded to makes genes accessible and allow them to be activated. The researchers used data from the ENCODE project to study a map of accessible parts of the human genome in different cell types. One of the things that they found was that virally-derived genes were much more common in these open regions than they were in the genome overall; in other words, the open regions were enriched in viral genes. When the researchers categorized these regions based on which other species we share them with, they discovered that most of the virally-derived open regions in our genome appeared during the evolution of primates.

This figure from the paper shows the open regions of our genome lined up with a tree according to which species have similar regions. The colours in the pie charts show the proportion of different genetic elements in open regions of our DNA. The purple fraction (labelled “LTR/ERV”) is the viral genes that have stowed away in our genome — and in the genomes of other primates.

Many of these old virus genes turned out to be promoters and other stretches of DNA that regulate gene activity. Most of the open regions also turned out to be specific to just a few cell types, suggesting that virally-derived genes might not just be important in making cells totipotent, but also in determining which genes are active in different types of cells. The researchers claim that their results show that infection by viruses which got incorporated into the genome “considerably transformed the transcriptional landscape during primate evolution”.

But that’s not the limit of what viruses have been credited with. The most exciting contribution they may have made is also the most contentious. Unlike bacteria, our cells store their DNA inside a nucleus, and some scientists believe that the nucleus may have originally been a virus which infected an ancient bacterium. Instead of copying itself and destroying the bacterium, it just took control of the cell’s machinery and, eventually, usurped the original genome. Patrick Forterre even believes that viruses may have been instrumental in the ancient switch from RNA to DNA. These are controversial suggestions and the jury’s still out, but one thing is certain: viruses have played a major role in shaping the evolution of life on Earth.